A problem quartered — new subtypes, new solutions?

Despite new drug approvals, pancreatic cancer remains one of the most-difficult-to-treat cancers, and the prognosis of patients with advanced-stage disease is dire. Now, the results of an integrated analysis of genomic, epigenetic, and transcriptomic data, generated by the Australian Pancreatic Cancer Genome Initiative as part of the International Cancer Genome Consortium (ICGC), have revealed that this disease entity comprises four discrete subtypes, each with distinct mechanisms of evolution that could be of potential therapeutic relevance.

Genomic analyses identified 32 recurrently mutated genes involved in 10 molecular pathways — aberrations in KRAS (92%), and genes involved in the G1–S cell-cycle checkpoint (78%) and TGF-β signalling (47%) were most common. Recurrent copy-number aberrations were also discovered, including many affecting known oncogenes (such as MET and NOTCH1) and tumour suppressors (CDKN2A, TP53, and BRCA1, for example).